The proposed project deals with mechanisms of reaction of the vascular wall to injury and the role of blood elements in these processes. Interactions of platelets with altered and normal endothelium will be studied in cell culture systems, using morphological and biochemical techniques. The structural and metabolic properties of endothelial cells responsible for their non-thrombogenic behavior, as well as potentially injurious and supportive interactions of platelets, will be examined. Vascular injury induced by platelet factors, chemicals, drugs, and environmental pollutants will be examined in vivo and in the endothelial culture system. Mechanisms and kinetics of endothelial proliferation in inflammation will be investigated. The role of inflammatory cells and mediators derived from these cells in modulating microvascular proliferation will be studied by examining endothelial growth in the cornea (corneal neovascularization) and endothelial proliferation in cell cultures. Special emphasis will be placed on the role of the activated macrophage in neovascularization. The biology and role of the endothelial cell surface coat, and its anionic sites will be studied in cell culture. These studies will be relevant to our understanding of thrombosis, atherosclerosis, and the pathogenesis of inflammatory diseases. BIBLIOGRAPHIC REFERENCES: Polverini, P.J., Cotran, R.S., and Sholley, M.M.: Endothelial proliferation in the delayed hypersensitivity reaction: An autoradiographic study. J. Immunol. 118:529-532, February, 1977. Sholley, M.D., Gimbrone, M.A., Jr., and Cotran, R.S.: Cellular migration and replication in endothelial regeneration: A study using irradiated endothelial cultures. Lab. Invest. 36:18, 1977.